Ginsenoside Rg3 is a tetracyclic-triterpene saponin compound existed in Ginseng, with a molecular weight of 784.13. There are two optical isomers for ginsenoside Rg3, ie. 20(R)-ginsenoside Rg3 and 20(S)-ginsenoside Rg3. 20(R)-ginsenoside Rg3 is chemically stable, and insoluble in water, while 20(S)-ginsenoside Rg3 is chemically unstable, and easily dissolvable in water. Their molecular structures are as follows:
The Molecular Structure of 20(R)-ginsenoside Rg3. The Molecular Structure of 20(S)-ginsenoside Rg3.
It is found that 20(R)-ginsenoside Rg3 has strong inhibitory and anti-metastatic activities to the tumor. As 20(R)-ginsenoside Rg3 is insoluble in water; the bioavailability of its oral preparations is very low, which greatly restricts the fulfillment of its clinical efficacy and its parenteral route of administration.
To dissolve the 20(R)-ginsenoside Rg3 in water, some studies have been explored, such as “Ginsenoside Rg3 hydroxypropyl-β-cyclodextrin clathrate, preparations and its processes” (Application No. 01119929.6), which was published in the Patent Bulletin on Jan. 29, 2003. The main content of the patent is as follows: Ginsenoside Rg3 hydroxypropyl-β-cyclodextrin clathrate, with a raw material weight ratio of ginsenoside:hydroxypropyl-β-cyclodextrin=1:1˜200. The preparation process as follows: (1) Dissolve the ginsenoside Rg3 in organic solvent; (2) Dissolve the hydroxypropyl-β-cyclodextrin in water; (3) Drip the ginsenoside solution to the hydroxypropyl-β-cyclodextrin solution, with vigorous stirring; after that continue stirring the mixture for another 2˜24 hours. Filter the mixture with a 0.45 μm micropore filter membrane, condense the filtrate, remove the organic solvent, redissolve in water for injection, and then filter the filtrate again with a 0.22 μm micropore filter membrane, lyophilize the filtrate to get a porous white powder, i.e. the ginsenoside clathrate.
The shortcomings of the method are as follows: (1) In the process of clathrate preparation, when the reactant (reactant solution) is recycled to a third of its original volume, there is still some residue of the organic solvent detected; however, it is ineffective to remove the residual organic solvent by lyophilization. Therefore, it is very difficult to meet the specification of the residual solvent in an injection solution when it is prepared with this clathrate powder. (2) In the process of clathrate preparation, the residual solvent is very helpful to form a dissolvable clathrate of ginsenoside Rg3 and hydroxypropyl-β-cyclodextrin, with a ratio of 1:1˜200. If the residual solvent is completely removed, there will be no stable clathrate formed under the above-mentioned range of ratio, and the ginsenoside Rg3 will be immediately separated as sediment from the aqueous clathrate, leaving the clathrate unsuitable for the preparation of injection solution. (3) Ginsenoside Rg3 could not be transformed to the clathrate completely with this method, and the utilization rate of the Rg3 is only 86%. Therefore, the cost of the production for making injection solution will be increased obviously.